Protective materials and bioactive drugs are used on medical devices for treating vascular conditions such as stents. With generally open cylindrical scaffolding, stents typically have apertured or lattice-like walls of a metallic or polymeric base, and can be either balloon expandable or self-expanding. A stent is typically deployed by mounting the stent on a balloon portion of a balloon catheter, positioning the stent in a body lumen, and expanding the stent by inflating the balloon. The balloon is then deflated and removed, leaving the stent in place. Stents help reduce the probability and degree of vessel blockage from restenosis.
Various approaches for providing localized drug delivery using coated stents have been under investigation and marketed for some time. A variety of stent coatings and compositions have been proposed to provide localized therapeutic pharmacological agents and treatment of a vessel at the site being supported by the stent. Stent coatings with various families of drug polymer chemistries have been used to increase the effectiveness of stenting procedures and to control drug-elution properties. For example, polymeric coatings can be made from polyurethane, polyester, polylactic acid, polyamino acid, polyorthoester, or polyphosphate ester. Examples of drug or bioactive agents include antirestonotic and anti-inflammatory compounds.
Medical research indicates a greater effectiveness of vascular stents when the stents are coated with pharmaceutical drugs that help prevent or treat medical conditions such as restenosis and thrombosis. These drugs may be released from a coating while in the body, delivering their patent effects at the site where they are most needed. The localized levels of the medications can be elevated, and therefore potentially more effective than orally or intravenously delivered drugs. Furthermore, drugs released from tailored stent coatings can have controlled, timed-release qualities, eluting their bioactive agents over hours, weeks or even months. Stent coatings typically have a drug or active agent, which has been dissolved or dispersed throughout the polymeric material and physically constrained within the polymer. The sustained release of drugs generally relies upon either controlled degradation of the polymer or diffusion through the polymer to control the elution of the compounds.
Stents can be coated with a polymer or combination of a polymer and a pharmaceutical agent or drug by application techniques such as dipping, spraying, painting, and brushing. Typical methods of coating, such as spraying, dipping and brushing techniques, can be susceptible to a degree of pooling, bridging, or webbing on stent structures and struts, problems recognized by those skilled in the art of manufacturing stents.
Several solutions have been suggested. One solution in a manual dipping process blows excessive material off an open stent framework, as disclosed in “Coating” by Taylor et al., U.S. Pat. No. 6,214,115 issued Apr. 10, 2001. The process addresses the problems of inconsistent drying and blockage of openings. Hossainy and others disclose another dipping process that addresses the issues of blockage and bridging between stent struts in “Process for Coating Stents”, U.S. Pat. No. 6,153,252 issued Nov. 28, 2000. Flow or movement of the coating fluid through the openings in the perforated medical device is used to avoid the formation of blockages or bridges. The flow system may use a perforated manifold inserted in the stent to circulate the coating fluid, or may place the stent on a mandrel or in a small tube that is moved relative to the stent during the coating process.
Another coating method that uses airflow is disclosed in “Coating Medical Devices Using Air Suspension”, Schwarz et al., International Patent Application WO 00/62830 published Oct. 26, 2000. The proposed method suspends a medical device in air and introduces a coating material into an air stream such that the material is dispersed therein to coat at least a portion of the device.
In addition to controlling any excessive coating material, an effective coating method needs to result in a lubricious or smooth outer surface of the coated stent, thereby reducing the probability of abrasions to body tissue as a stent is deployed. One coating method that optionally applies a solvent by dipping or spraying on an already coated stent to smooth the outer surface of the coating is described by Ding in “Method of Applying Drug-Release Coatings”, U.S. Pat. No. 5,980,972 issued Nov. 9, 1999. The method uses two solutions: one with a polymer dissolved in a first solvent and another with a drug dissolved or suspended in a second solvent. When a third solvent is used to smooth the stent coating, the solvent needs to be compatible with the polymer matrix.
In another example, a collagen liner material forms a lubricious surface over the stent to protect the vascular wall and form a non-thrombogenic cushion for the stent in the vascular lumen, as disclosed in “Stent with Collagen”, Buirge et al., U.S. Pat. No. 5,693,085 issued Dec. 2, 1997.
Another smooth stent surface is described in “Stent Lining”, Sahatjian et al., U.S. Pat. No. 6,364,893, issued Apr. 2, 2002. A stent is lined with a hydrogel to reduce shear forces and flow disturbances in the blood, to protect damaged cells adjacent to the stent, to reduce platelet deposition at the stent site, and to deliver a drug to reduce or prevent restenosis of stent lumens. The expandable stent is mounted on a catheter balloon, which is coated with a hydrogel. The stent is delivered in a contracted condition to a targeted site in a body where the expanding balloon lodges the stent in the body with the hydrogel coated on the inner surfaces of the stent as a lining.
Drug polymer coatings on medical devices need to adhere well to the substrate or surface of the medical device and be mechanically pliant, because the devices often undergo significant flexion or expansion during the delivery and deployment. Excess coating material that can occur between struts of the stent needs to be removed or controlled to prevent cracking or flaking during or after the deployment of the stent. A stent deployed by self-expansion or balloon expansion is accompanied by a high level of bending at portions of the stent framework, which can cause cracking, flaking, peeling, or delaminating of many candidate drug polymers when the stent diameter is increased by threefold or more during expansion. In addition, any step within the process for coating a pre-deployed stent should not cause a drug-polymer to fall off, crystallize or melt.
Accordingly, a desirable, efficient and improved coating method would provide a well-adhered coating with a smooth outer surface of a medical device. In addition, the method would minimize or eliminate the pooling, bridging, or webbing of excess coating material between structures such as stent struts. In addition, the stent associated with this method has a smoother coating topography with one or more well adhered drug-polymer coatings that maintain mechanical integrity during stent deployment and provide a desired elution rate for one or more drugs, overcoming the deficiencies and limitations described above.